Objective: To analyze the level of PCDD/Fs exposure of occupational workers in the waste incineration industry and explore the risk of occupational exposure. Methods: In September 2021, literature on environmental PCDD/Fs exposure in waste incineration plants published from the establishment of the database to February 10, 2021 was retrieved from CNKI database. A total of 1365 literatures were retrieved, and 7 met the criteria for inclusion. The US Environmental Protection Agency (EPA) inhalation risk model was used to assess and analyze carcinogenic and non-carcinogenic risks of PCDD/Fs exposure among occupational workers in the waste incineration industry. Results: A total of 86 sampling sites were included in incineration plants in 7 regions. The study of Wuhan area showed that the concentration of working environment near the waste incinerator in the same factory was the highest, followed by the rest and office area in the factory. The concentration of PCDD/Fs in waste incinerators was the highest in Southwest China (4880.00-24880.00 pg TEQ/m(3)), and the lowest in Shenzhen (0.02-0.44 pg TEQ/m(3)). According to the cancer risk assessment, with the increase of exposure years, the risk of cancer increased. The highest risk of cancer was found in the waste incineration plants in Southwest China. When the exposure period was 1 year, the risk was moderate (22.40×10(-6)-114.20×10(-6)). When the exposure time was more than 5 years, the risk of cancer was high. In Jinan, workers working near the incinerator had a moderate risk of cancer after five years of exposure. In Zhejiang, workers were at medium risk of cancer after exposure for more than 20 years. Workers in Wuhan, Shanghai, Zhejiang Province, Shenzhen and the Pearl River Delta were still at low risk of cancer after 40 years of occupational exposure. HQ>1 of workers working near the waste incinerators in Jinan, Zhejiang Province and Southwest China, and the qualitative evaluation results showed that the non-carcinogenic risk was unacceptable. Conclusion: There are great differences in PCDD/Fs of occupational exposure in waste incineration industry, and the occupational exposure exceeding the occupational exposure limit has higher carcinogenic and non carcinogenic risks.
Humans ; Dibenzofurans ; Polychlorinated Dibenzodioxins/analysis* ; Air Pollutants/analysis* ; Incineration ; Dibenzofurans, Polychlorinated/analysis* ; China/epidemiology* ; Benzofurans ; Occupational Exposure/analysis* ; Carcinogens ; Risk Assessment ; Neoplasms ; Environmental Monitoring/methods*

Objective: To investigate the association between Helicobacter pylori (Hp) virulence factor genotypes and the degree and activity of gastric mucosa pathological changes in pediatric gastroduodenal diseases. Methods: This retrospective cohort study was conducted from May 2020 to October 2020. The frozen strains of Hp, which were cultured with the gastric mucosa of 68 children with gastroscopy confirmed gastroduodenal diseases who visited the children's hospital of Zhejiang University School of Medicine from April 2012 to December 2014, were resuscitated. After extracting DNA from these Hp strains, PCR amplification and agarose gel electrophoresis were performed to determine the detection rate of cytotoxin-associated protein A (cagA),vacuolating cytotoxin A (vacA)(s1a、s1b/s2,m1/m2), outer inflammatory protein A (oipA),blood group antigen binding adhesin (babA),duodenal ulcer promoting protein A (dupA) genes; oipA genes were sequenced to determine the gene status. The patients were divided into different groups according to the findings of gastroscopy and gastric mucosa pathology. The detection rates of various virulence factor genotypes among different groups were compared using χ² tests or Fisher's exact tests. Results: The 68 Hp strains all completed genetic testing. According to the diagnostic findings of gastroscopy, the 68 cases were divided into 47 cases of superficial gastritis and 21 cases of peptic ulcer. Regarding the pathological changes of gastric mucosa, 8 cases were mild, and 60 cases were moderate and severe according to the degree of inflammation; 61 cases were active and 7 cases inactive according to the activity of inflammation. The overall detection rates of cagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA virulence factor genes were 100% (68/68), 100% (68/68), 94% (64/68), 99% (67/68), 82% (56/68), and 71% (48/68), respectively. In the superficial gastritis group, their detection rates were 100% (47/47), 100% (47/47), 96% (45/47), 98% (46/47), 81% (38/47), and 70% (33/47), respectively; in the peptic ulcer group, their detection rates were 100% (21/21), 100% (21/21), 90% (19/21), 100% (21/21), 86% (18/21), and 71% (15/21), respectively. There was no statistically significant difference between the two groups (all P>0.05). In the mild gastric mucosa inflammation group, the detection rates of the above six genotypes were 8/8, 8/8, 8/8, 7/8, 7/8, and 5/8, respectively; and in the moderate to severe inflammation groups, the detection rates were 100% (60/60), 100% (60/60), 93% (56/60), 100% (60/60), 82% (49/60), and 72% (43/60), respectively, with no statistically significant difference between the two groups (all P>0.05). In the active inflammation group, the detection rate of six genotypes were 100% (61/61), 100% (61/61), 93% (57/61), 98% (60/61), 82% (50/61), and 72% (44/61), respectively; and in the inactive inflammation group, they were 7/7, 7/7, 7/7, 7/7, 6/7, and 4/7, respectively. Again, there was no statistically significant difference between the two groups (all P>0.05). There was no statistically significant difference in the detection rate of combinations of 4 or 5 virulence factor genes among the different groups (all P>0.05). Conclusions: CagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA genes are not associated with superficial gastritis and peptic ulcer in children, or with the degree and activity of gastric mucosa pathological inflammation. Different gene combinations of cagA, vacA, oipA, babA2, and dupA have no significant effects on predicting the clinical outcome of Hp infection in children.
Humans ; Child ; Helicobacter pylori/genetics* ; Retrospective Studies ; Genotype ; Inflammation ; Gastritis ; Cytotoxins

OBJECTIVE: To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ). METHODS: Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated. RESULTS: DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin. CONCLUSIONS The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.
Animals ; Male ; Rats ; Diquat/toxicity* ; Gastrointestinal Diseases ; Intestines ; Poisons ; Rats, Wistar ; Toxicokinetics

Objective: To investigate the effect of arsenic and its main metabolites on the apoptosis of human lung adenocarcinoma cell line A549 and the expression of pro-apoptotic genes Bad and Bik. Methods: In October 2020, A549 cells were recovered and cultured, and the cell viability was detected by the cell counting reagent CCK-8 to determine the concentration and time of sodium arsenite exposure to A549. The study was divided into NaAsO(2) exposure groups and metobol: le expoure groups: the metabolite comparison groups were subdivided into the control group, the monomethylarsinic acid exposure group (60 μmol/L) , and the dimethylarsinic acid exposure group (60 μmol/L) ; sodium arsenite dose groups were subdivided into 4 groups: control group (0) , 20, 40, 60 μmol/L sodium arsenite NaAsO(2). Hoechst 33342/propidium iodide double staining (Ho/PI) was used to observe cell apoptosis and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of Bad and Bik mRNA in cells after exposure. Western blotting was used to detect the protein expressions of Bad, P-Bad-S112, Bik, cleaved Bik and downstream proteins poly ADP-ribose polymerase PARP1 and cytochrome C (Cyt-C) , using spectrophotometry to detect the activity changes of caspase 3, 6, 8, 9. Results: Compared with the control group, the proportion of apoptotic cells in the 20, 40, and 60 μmol/L NaAsO(2) dose groups increased significantly (P<0.01) , and the expression levels of Bad, Bik mRNA, the protein expression levels of Bad, P-Bad-S112, Bik, cleaved Bik, PARP1, Cyt-C were increased (all P<0.05) , and the activities of Caspase 3, 6, 8, and 9 were significantly increased with significantly differences (P<0.05) . Compared with the control group, the expression level of Bad mRNA in the DMA exposure group (1.439±0.173) was increased with a significant difference (P=0.024) , but there was no significant difference in the expression level of Bik mRNA (P=0.788) . There was no significant differences in the expression levels of Bad and Bik mRNA in the poison groups (P=0.085, 0.063) . Compared with the control group, the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to MMA were 0.696±0.023, 0.707±0.014, 0.907±0.031, 1.032±0.016, and there was no significant difference between the two groups (P=0.469, 0.669, 0.859, 0.771) ; the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to DMA were 0.698±0.030, 0.705±0.022, 0.908±0.015, 1.029±0.010, and there was no difference between the two groups (P=0.479, 0.636, 0.803, 0.984) . Conclusion: Sodium arsenite induces the overexpression of Bad and Bik proteins, initiates the negative feedback regulation of phosphorylated Bad and the degradation of Bik, activates the downstream proteins PARP1, Cyt-C and Caspase pathways, and mediates the apoptosis of A549 cells.
A549 Cells ; Adenosine Diphosphate Ribose/pharmacology* ; Apoptosis ; Apoptosis Regulatory Proteins ; Arsenic ; Arsenites ; Cacodylic Acid/pharmacology* ; Caspase 3 ; Caspases/pharmacology* ; Cytochromes c/pharmacology* ; Humans ; Mitochondrial Proteins/pharmacology* ; Poisons ; Propidium/pharmacology* ; RNA, Messenger ; Sincalide/pharmacology* ; Sodium Compounds ; bcl-Associated Death Protein/metabolism*

Objective: To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM). Methods: GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay. Results: Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation. Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.
Antineoplastic Agents, Alkylating/therapeutic use* ; Brain Neoplasms/metabolism* ; Cell Line, Tumor ; DNA/therapeutic use* ; Glioblastoma/metabolism* ; Humans ; Radiation, Ionizing ; Temozolomide/therapeutic use*

In 2020, the mass concentration of PM_2.5 in Shijiazhuang urban area was(80.30±71.43)μg/m³. The Spearman correlation analysis between metals and metalloids showed that Sb with Cd, Pb, Ni, Se, Cd with Pb, Ni, Se, Pb with Ni, Se, Ni with Se, and Se with Tl were positively correlated, with a coefficient greater than 0.5. The main sources of metals and metalloids of PM_2.5 were traffic emissions, fuel combustion, metal smelting and dust. The HQ values of Pb, Hg and Mn for each population were less than 1, with lower non-carcinogenic risk. The R values of carcinogenic risk of Ni and Cd in each population were less than 1×10^-6, which could be acceptable risk level for the population. The R values of carcinogenic risk of As and Cr in different populations were between 1×10^-6 and 1×10^-4, with potential carcinogenic risk, particularly higher in adult males.
Adult ; Cadmium ; Carcinogens/analysis* ; Dust/analysis* ; Environmental Monitoring ; Humans ; Lead ; Male ; Metalloids/analysis* ; Risk Assessment

As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.
Ado-Trastuzumab Emtansine/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/therapy* ; Camptothecin/adverse effects* ; Consensus ; Cytotoxins/therapeutic use* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Neutropenia/etiology* ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/therapy* ; Ventricular Function, Left

The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.
Animals ; Anticonvulsants/therapeutic use* ; Neurotoxins/pharmacology* ; Scorpion Venoms/pharmacology* ; Scorpions/chemistry* ; Voltage-Gated Sodium Channels

The present study aims to investigate the correlation between irritant toxicity variation and lectin content variation during the processing of Pinelliae Rhizoma products and to explore the feasibility of Western blot as a method for the detection of lectin. We processed Pinelliae Rhizoma Praeparatum Cum Alumine, Pinelliae Rhizoma Praeparatum, and Pinelliae Rhizoma Praeparatumcum Zingibere et Alumine to different degrees and then analyzed their irritant toxicity via Draize rabbit eye test. Western blot was employed to determine the lectin content in Pinelliae Rhizoma products processed with different methods. The correlation between toxicity variation and lectin content variation was then analyzed. Different decoction pieces of Pinelliae Rhizoma were collected for the determination of lectin content. The three processed products of Pinelliae Rhizoma showed gradually decreased toxicity and lectin content as the processing continued. The decreasing trend of lectin content was consistent with that of irritant toxicity during processing, which indicated that the change in lectin content could reflect the trend of irritant toxicity. No band of lectin appeared in the Western blot of processed products of Pinelliae Rhizoma, which suggested that western blotting can be used for the detection of toxic lectin in the processed products of Pinelliae Rhizoma. Lectin should not be detected in the Pinelliae Rhizoma products processed according to the methods in the Chinese Pharmacopoeia.
Animals ; Drugs, Chinese Herbal/toxicity* ; Irritants ; Lectins ; Pinellia ; Rabbits ; Technology, Pharmaceutical/methods*

OBJECTIVES: To retrospectively analyze homicide cases of death after injection and provide reference for forensic identification. METHODS: Six homicide cases of death after injection which were investigated by the Criminal Investigation Team of Shanghai Public Security Bureau were collected and analyzed, including case situation, scene investigation, autopsy and other materials. RESULTS: The 6 cases were premeditated crimes, 5 cases took place in private spaces, and 5 cases involved the victims approached by suspects' decoy. There were no obvious abnormalities at the scene of the 6 cases. In 6 cases, the victim's body surface injury was mild or no, lividity color was abnormal, and the needlestick injury showed different manifestations from conventional medical measures. CONCLUSIONS Death after injection is a highly concealed crime and easy to be ignored. For the suspected injection injury found in autopsy, it is necessary to carefully examine, identify and analyze, be alert to the situation of injecting poison (drug) and do a good job in evidence fixation and material extraction.
Autopsy ; China/epidemiology* ; Homicide ; Poisons ; Retrospective Studies